TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32681	98266;98267;98268	chr2:178540125;178540124;178540123	chr2:179404852;179404851;179404850
N2AB	31040	93343;93344;93345	chr2:178540125;178540124;178540123	chr2:179404852;179404851;179404850
N2A	30113	90562;90563;90564	chr2:178540125;178540124;178540123	chr2:179404852;179404851;179404850
N2B	23616	71071;71072;71073	chr2:178540125;178540124;178540123	chr2:179404852;179404851;179404850
Novex-1	23741	71446;71447;71448	chr2:178540125;178540124;178540123	chr2:179404852;179404851;179404850
Novex-2	23808	71647;71648;71649	chr2:178540125;178540124;178540123	chr2:179404852;179404851;179404850
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Fn3-126
• Domain position: 82
• Structural Position: 114
• Q(SASA): 0.5173
• Predicted PPI site: I

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
G/D	None	None	1.0	N	0.789	0.42	0.277730125212	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
G/A	0.1146	likely_benign	0.1409	benign	-0.251	Destabilizing	1.0	D	0.689	prob.neutral	N	0.358461001	None	None	I
G/C	0.373	ambiguous	0.4334	ambiguous	-0.805	Destabilizing	1.0	D	0.818	deleterious	N	0.475712246	None	None	I
G/D	0.828	likely_pathogenic	0.8825	pathogenic	-0.768	Destabilizing	1.0	D	0.789	deleterious	N	0.484926376	None	None	I
G/E	0.7253	likely_pathogenic	0.807	pathogenic	-0.944	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	I
G/F	0.8437	likely_pathogenic	0.8776	pathogenic	-1.049	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	I
G/H	0.8613	likely_pathogenic	0.8989	pathogenic	-0.476	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
G/I	0.4946	ambiguous	0.5644	pathogenic	-0.445	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	I
G/K	0.8634	likely_pathogenic	0.9049	pathogenic	-0.812	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	I
G/L	0.7129	likely_pathogenic	0.7687	pathogenic	-0.445	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	I
G/M	0.7311	likely_pathogenic	0.7797	pathogenic	-0.442	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	I
G/N	0.768	likely_pathogenic	0.8135	pathogenic	-0.404	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
G/P	0.9825	likely_pathogenic	0.9851	pathogenic	-0.349	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	I
G/Q	0.7566	likely_pathogenic	0.8138	pathogenic	-0.735	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	I
G/R	0.6997	likely_pathogenic	0.7671	pathogenic	-0.307	Destabilizing	1.0	D	0.845	deleterious	N	0.489044116	None	None	I
G/S	0.2031	likely_benign	0.2521	benign	-0.502	Destabilizing	1.0	D	0.789	deleterious	N	0.458241206	None	None	I
G/T	0.45	ambiguous	0.518	ambiguous	-0.619	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	I
G/V	0.3129	likely_benign	0.3679	ambiguous	-0.349	Destabilizing	1.0	D	0.839	deleterious	N	0.39103478	None	None	I
G/W	0.834	likely_pathogenic	0.8664	pathogenic	-1.184	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
G/Y	0.8264	likely_pathogenic	0.8722	pathogenic	-0.845	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.